| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
-hydroxysteroid Dehydrogenase and COX-2 in the Kidney
1 George O'Brien Center for Kidney and Urologic Diseases and Department of Medicine, Vanderbilt University School of Medicine and Department of Veterans Affairs, Nashville, TN, USA
2 George O'Brien Center for Kidney and Urologic Diseases and Department of Medicine, Vanderbilt University School of Medicine and Department of Veterans Affairs, Nashville, TN, USA; Cell and Developmental Biology, Vanderbilt University School of Medicine and Department of Veterans Affairs, Nashville, TN, USA
* To whom correspondence should be addressed. E-mail: ray.harris{at}vanderbilt.edu.
The syndrome of apparent mineralocorticoid excess (SAME) is an autosomal recessive form of salt-sensitive hypertension caused by deficiency of the kidney type 2 11
-hydroxysteroid dehydrogenase (11HSD2). In this disorder, cortisol is not inactivated by 11HSD2, occupies mineralocorticoid receptors (MRs), and causes excessive sodium retention and hypertension. In renal medulla, prostaglandins derived from cyclooxygenase-2 (COX-2) stimulate sodium and water excretion and renal medullary COX-2 expression increases after mineralocorticoid administration. We investigated whether medullary COX-2 also increases in rats with 11HSD2 inhibition and examined its possible role in the development of hypertension. 11HSD2 inhibition increased medullary and decreased cortical COX-2 expression in adult rats and induced high blood pressure in high salt treated rats. COX-2 inhibition had no effect on blood pressure in control animals, but further increased blood pressure in high salt treated rats with 11HSD2 inhibition. COX-1 inhibition had no effect on blood pressure in either control or experimental animals. 11HSD2 inhibition also led to medullary COX-2 increase and cortical COX-2 decrease in weaning rats primarily through activation of MR. In the suckling rats, medullary COX-2 expression is very low, consistent with a urinary concentrating defect. 11HSD2 inhibition had no effect on either cortical or medullary COX-2 expression in the suckling rats, consistent with low levels of circulating corticosterone in these animals. These data indicate that COX-2 plays a modulating role in the development of hypertension due to 11HSD2 deficiency, and 11HSD2 regulates renal COX-2 expression by preventing glucocorticoid access to MRs during postnatal development.
This article has been cited by other articles:
|
|
 |
|
  B. Yao, R. C. Harris, and M.-Z. Zhang Intrarenal Dopamine Attenuates Deoxycorticosterone Acetate/High Salt-Induced Blood Pressure Elevation in Part Through Activation of a Medullary Cyclooxygenase 2 Pathway Hypertension, November 1, 2009; 54(5): 1077 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Brennan, S. Kaufman, S. W. Reynolds, B. T. McCook, G. Kan, I. Christiaens, M. E. Symonds, and D. M. Olson Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R197 - R205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Li, L. Chen, F. Yi, M. Xia, and P.-L. Li Salt-Sensitive Hypertension Induced by Decoy of Transcription Factor Hypoxia-Inducible Factor-1{alpha} in the Renal Medulla Circ. Res., May 9, 2008; 102(9): 1101 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Baserga, M. A. Hale, Z. M. Wang, X. Yu, C. W. Callaway, R. A. McKnight, and R. H. Lane Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1943 - R1955. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
